We have developed a sensitive, rapid and non-radioactive in vitro assay to screen diet-derived compounds for estrogen-like activity by monitoring the expression of pS2 mRNA in MCF-7 human breast cancer cells. Using our method we successfully identified several compounds, including NDGA, daidzein, genistein, equol, and kaempferol as being estrogenic. Our results were recently published in Cancer Research (Vol. 54, 1994). The isoflavones daidzein and genistein are major components of soy food; equol is derived from daidzein by the action of gut microflora. Epidemiological evidence indicates that increased consumption of soy foods is associated with lowered risk for hormone dependent cancers. It has been postulated that these compounds contribute to beneficial effects of soy food. We were interested in studying the molecular mechanism by which they exert their effects. We examined the ability of the various compounds to compete with estradiol for binding to the estrogen receptor. The estrogenic compounds like daidzein, equol, and genistein were also very effective in displacing labeled estradiol from binding to the estrogen receptor. The expression of estrogen receptor mRNA in MCF-7 cells in response to long term exposure to genistein was also evaluated. We have two manuscripts ready for submission based on this work. We are currently studying the effect of the isoflavones on the expression of TGF-beta levels in MCF-7 cells using a Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) method.